Guidelines for initiating therapeutic mild hypothermia ...

of 12 Title: Investigation of Neonatal Hypotonia Contact: Clinical Guidelines Lead

V: 2 Approved by: Neonatal Guidelines Group and Neonatal Governance Group: January 2022 Next Review: January 2025 Trust Ref No: C34/2020 NB: Paper copies of this document may not be most recent version. The definitive version is held on InSite in the Policies and Guidelines Library and on BadgerNet

1. Introduction and Who Guideline applies to

This guideline is aimed at all Health care professionals involved in the care of infants within the Neonatal Service.

Key Points

• Neonatal hypotonia (the ‘floppy infant’) is an important clinical presentation in the newborn period with a wide differential diagnosis

• Investigations need to be guided by the history and examination findings

• The Neonatal Hypotonia Investigations Checklist (Appendix 1) should be used to keep a record of the samples sent and the results obtained.

Aim

This guideline offers a stepwise approach to the assessment and investigation of newborn infants with hypotonia to aid diagnosis without unnecessary investigations.

Contents 1. Introduction and Who Guideline applies to ............................................................. 1 2. Guideline Standards and Procedures ..................................................................... 2

Aetiology of Neonatal Hypotonia and Definitions: ................................................... 2 Table 1 Causes of Hypotonia by Anatomical Site ................................................... 3

History taking .......................................................................................................... 4 Clinical Examination ............................................................................................... 5 Investigations .......................................................................................................... 6

Fig 1. History, Examination and Investigations flowchart ........................................ 8 3. Education & training ............................................................................................... 9

4. Audit Criteria .......................................................................................................... 9 5. Supporting References ........................................................................................... 9 6. Key Words .............................................................................................................. 9

Contact and review details ...................................................................................... 9 Appendix 1: Neonatal Hypotonia Investigations Checklist .................................... 10

Assessment and Investigation of Neonatal Hypotonia

(the ‘Floppy Infant’) Jan 2022 – Jan 2025 C34/2020

http://insitetogether.xuhl-tr.nhs.uk/pag/Pages/default.aspx




2. Guideline Standards and Procedures

Background

The floppy infant represents a diagnostic challenge. This is firstly because there are

a wide range of differential diagnoses – including central or peripheral nervous

system abnormalities, muscle disorders, genetic disorders, endocrinopathies and

metabolic diseases. Hypotonia may also be a transient phenomenon seen in acute

illness or prematurity. Secondly, when a decision is made to investigate these babies

further, the tests required may be extensive, which means following up results and

keeping track of what has been requested can be difficult. Therefore, a systematic

approach to assessment and investigation is required.

Aetiology of Neonatal Hypotonia and Definitions:

The causes of Neonatal Hypotonia can be subdivided into Central causes (80% of

cases - brain, spinal cord, but excluding the motor neurone) and Peripheral causes

(lower motor neuron including motor neurone, axon, neuromuscular junction and

muscle).

Hypotonia: A reduced resistance to passive movements, which may be accompanied by an increased range of movements around the joints. Hypotonia is often identified by an abnormal posture (e.g. frog-leg posture), and there can be associated weakness.

Weakness: A reduction in the muscle power that can be generated (e.g. lack of

muscle movement against gravity).

Hypotonia (floppy) without weakness: Where there is hypotonia but strength is relatively preserved (e.g. anti-gravity limb movements are present), a CENTRAL cause of hypotonia is more likely.

Hypotonia with weakness: Hypotonia accompanied by weakness is more suggestive

of a PERIPHERAL, neuromuscular cause. In such cases, reflexes are often reduced

or absent. (Table 1)





Table 1 Causes of Hypotonia by Anatomical Site Site Causes Floppy -

preserved strength

Floppy and

Weak

Central causes (80% of all cases)

Brain Acute

• Hypoxic-ischaemic encephalopathy

• Acquired and congenital infections causing encephalopathy

• Intracranial haemorrhage

• Drug effects

Chronic

• Chromosomal abnormalities (e.g. Down syndrome and Prader-Willi syndrome)

• Cerebral structural malformations

• Inborn errors of metabolism (e.g. Zellweger syndrome)

Spinal cord • Birth trauma to spinal cord

Peripheral neuromuscular causes

Anterior horn cell • Spinal muscular atrophy

Neuromuscular junction

• Transient acquired myasthenia gravis

• Congenital myasthenia

• Infantile botulism

Peripheral nerves

• Congenital demyelinating neuropathy

• Hypomyelinating neuropathy

• Hypomyelinating neuropathy

• Axonal neuropathy

• Guillain-Barré syndrome

Muscle • Muscular dystrophies

• Congenital myopathies

• Myotonic dystrophy and congenital myotonias

• Endocrine myopathy e.g. hypothyroidism

• Metabolic myopathies (e.g. Glycogen storage diseases)

• Energy depletion - muscle mitochondria e.g. fatty acid oxidation and carnitine disorders, respiratory chain disorders

Connective tissue disorders

• Ehler Danlos syndrome

• Marfan syndrome

• Osteogenesis imperfecta




History taking Important aspects to consider during history taking are: Antenatal

• Maternal disease: ▪ Diabetes, epilepsy, myotonic dystrophy, myasthenia

• Previous pregnancies: ▪ Stillbirths, childhood deaths

• This pregnancy: ▪ Maternal drug use (prescribed or recreational) ▪ Antenatal infection ▪ Screening risk for Trisomies ▪ Decreased fetal movements, abnormal presentation and oligo/ polyhydramnios

Perinatal

• Apgar scores

• Resuscitation required

• Cord gases

• Risk factors for sepsis Postnatal

• Character of cry – a weak cry may be seen in infants with neuromuscular weakness

• Respiratory effort

• Ability to feed

• Level of alertness

• Level of spontaneous activity

• Seizures





Clinical Examination

A thorough systems based clinical examination with recording of baseline observations is required. Neurological examination should include the features detailed in Table 2, including assessment for any dysmorphic features. While clinical examination can be helpful in indicating whether a central or peripheral cause is more likely, there can be overlap between the findings in some conditions.

Table 2: Examination findings associated with Central and Peripheral Hypotonia

(SMA – spinal muscular atrophy)

The following table summarises the likely examination findings depending on the area or anatomical site of the nervous system affected:

Table 3: Clinical findings by anatomical site





Investigations (see Fig. 1)

Blood Count and Routine Biochemistry

Baseline blood tests including FBC, U&Es,CRP,LFT and bone profile (including

calcium and magnesium) are important in excluding infection and electrolyte

disturbances as causes for hypotonia. Thyroxine (T4) and TSH should be checked,

looking for evidence of congenital hypothyroidism. Creatine Kinase (CK) is an

enzyme found in muscles. Increased amounts of CK are released into the blood

when there is muscle damage. Levels are therefore raised in Congenital Muscular

Dystrophy (5 to 10 times normal). However, it is important to be aware that CK levels

can be raised in the first hours of life and also increase with acidosis - for example

following Hypoxic Ischaemic Encephalopathy (HIE). Therefore, if CK is raised in an

early sample, it is worth repeating it after a few days. CK levels should also be taken

prior to Electromyography (EMG) studies or muscle biopsies as these can cause

raised levels. In cases of multisystemic involvement, screening for inborn errors of

metabolism is recommended.

Genetic Testing

Should be chosen according to clinical presentation and presence of any dysmorphic

features. A Rapid FISH Screen can be requested for trisomies - these results are

usually available within 48 hours. Microarray results take 2 weeks for a neonate (less

than 28 days of age) and 4-6 weeks for a baby over 28 days old. Molecular genetics:

these samples are sent to Nottingham. If requested, the molecular genetics team

can conduct a ‘Floppy Infant Screen.’ This includes testing for three conditions -

Prader Willi Syndrome, Myotonic Dystrophy and Spinal Muscular Atrophy. Please

ensure you specify this on the form. It is useful to send a separate EDTA bottle for

DNA storage in case further testing is required in the future.

Lumbar puncture

Cerebrospinal fluid (CSF) can be examined for evidence of infection. Raised protein

levels may also be suggestive of peripheral neuropathy or neurodegenerative

disease.

Imaging

Chest x-ray may show cardiomegaly which is suggestive of possible

cardiomyopathy. Thin ribs at birth may be seen in neuromuscular conditions. In

terms of neuroimaging, floppy babies should undergo a cranial ultrasound scan on

the neonatal unit. This may initially be performed by a neonatologist to rule out acute

changes, although a scan by a radiologist is also needed.





Cranial ultrasound can identify gross abnormalities of brain structure. It is likely that

in such infants, further imaging (usually MRI head and spine) will be needed. These

scans are helpful in the identification of structural malformations, neuronal migration

defects, brain stem and cerebellar abnormalities, and can identify features

suggestive of mitochondrial abnormalities and metabolic diseases. Requests for

such scans should be discussed with the radiology team.

Electrophysiological studies

Seizures and encephalopathy may be identified by EEG. On the neonatal unit, CFM

(aEEG) can be used to classify the background cerebral activity and to detect

seizures over longer periods of time. Electromyograms (EMGs) and nerve

conduction studies are useful in diagnosing disorders of the lower motor neurone

unit (disorders of either the muscle, neuromuscular junction or peripheral nerves.)

Nerve conduction studies produce consistent and reliable results after 32 weeks of

gestation. These investigations can be booked on the ICE system although it is best

to also discuss them with the neurophysiology team by telephone.

Muscle biopsies

Neonatal muscle biopsy results are difficult to interpret and therefore biopsies may

be delayed until babies are around 6 months of age, depending upon the clinical

picture.

Multidisciplinary team assessment

Involvement of other clinical teams may be sought - these may include neurology,

respiratory, cardiology, ENT, renal, ophthalmology and metabolic. In cases where

there are dysmorphic features but no clear unifying diagnosis, it is useful to refer to

the clinical genetics team for a ward review. Referral to the above specialities is a

consultant-led decision.





Fig 1. History, Examination and Investigations flowchart Please see Appendix 1: Neonatal Hypotonia Checklist for sample details.




3. Education & training

None

4. Audit Criteria

1. Neurological Examination should be recorded in the notes (100%) 2. Investigations checklist used to record investigations sent and results

received (100%)

5. Supporting References

1. Newborn Services Clinical Guideline: Neonatal Hypotonia, Auckland District

Health Board

2. Ahmed MI, Iqbal M, Hussain N. A structured approach to the assessment of a

floppy neonate. J Pediatr Neurosci 2016;11:2-6

3. Miralles R, Panjwani D. Neonatal Hypotonia. In Emerging Topics and

Controversies in Neonatology. Boyle EM, Cusack J (eds.). Springer Nature

Switzerland AG 2020

6. Key Words

Central hypotonia, Generalised hypotonia, Neurological, Peripheral hypotonia

________________________________________________________

The Trust recognises the diversity of the local community it serves. Our aim therefore is to provide a safe environment free from discrimination and treat all individuals fairly with dignity and appropriately according to their needs. As part of its development, this policy and its impact on equality have been reviewed and no detriment was identified.

Contact and review details

Guideline Lead (Name and Title) Sumit Mittal - Consultant

Executive Lead Chief Nurse

Original Author Jennifer Mann, Robin Miralles

Details of Changes made during review:

Date Issue Number

Reviewed By Description Of Changes (If Any)

Feb 2020 1

June 2020 1 Neonatal Guideline and Governance Group

Jan 2022 2 Neonatal Guideline and Governance Group

No changes





Appendix 1: Neonatal Hypotonia Investigations Checklist

Investigation Tick if required

Sample requirements Date sent/req

Turn around

Result Date of result

Baseline bloods

Full blood count 0.5ml EDTA bottle Hours

U&Es and CRP

0.5ml lithium heparin bottle for all

Hours

LFTs Hours

Bone profile Hours

T4 and TSH 0.5ml white bottle Hours

Creatine Kinase 0.5ml lithium heparin bottle Hours

Infection screen

Blood culture 1ml in blood culture bottle 2 days

CSF MCS 3 white top bottles with 5 drops CSF in each. 1 yellow bottle. Consider discussing with neurology prior to LP in case further samples are required

2 days

CSF protein and glucose

Hours

Genetics: Please note the genetics lab is only open 9am-5pm therefore send during daytime hours

Rapid FISH 1.2 lithium heparin bottle and 1.2ml EDTA bottle

2 days

Microarray 14 days






Turn around


Molecular genetics 1.2 ml EDTA bottle: Floppy baby screen -Prader Willi, Myotonic Dystrophy and SMA

2 weeks

DNA for storage 1.2ml EDTA bottle n/a

Metabolic screen: Please note special chemistry lab is only open 9am-5pm therefore collect and send during daytime hours

Blood gas with glucose and lactate

1 cap gas tube test on unit Minutes

Ammonia 1.2ml lithium heparin-to lab on ice within 30 minutes

Hours

Ketones Ketone meter or urine dipstick Bedside

Amino acids 1.2ml lithium heparin bottle 2 weeks

Organic acids Urine plain white top 5ml 2 weeks

Acylcarnitine profile 1.2ml lithium heparin bottle 2 weeks

Free fatty acids 1.2ml yellow top bottle 2 weeks

Very Long Chain FA 1.2ml lithium heparin bottle 2 weeks

Glycosaminoglycans Urine plain white top 5ml 2 weeks

Imaging

Chest x-ray Request on ICE and discuss as required with the Radiology team

n/a

Cranial US n/a

MRI /CT head n/a






Turn around


Neurophysiology tests

EEG Request on ICE and discuss with the Neurophysiology team

n/a

EMG n/a

Nerve conduction study

n/a

Other tests


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